Antibodies selection criteria

In practice, the ability to generate antibodies having particular properties from libraries is limited by the screen that is employed. Initial screens for affinity and/or specificity are used to reduce the number of potential hits from the initial hbrary of 10 ° to 10 -10 which must then be screened for a particular biological function. As delineated above, the (usually few) binders with a biological effect can then be affinity matured, such that affinity does not have to be an initial selection criterion. HuCAL thus provides a systematic means of screening large parts of sequence and... 

Traditionally, the desired monoclonal antibody is selected on the basis of binding affinity to the TSA. This approach led to a multitude of effective catalytic antibodies, the rate acceleration of which, however, is usually orders of magnitude below that of comparable enzymes. Furthermore, detailed mechanistic investigations often revealed a different catalysis mechanism than originally assumed. A different approach for the selection of catalytic antibodies is the reactive immunization where the selection criterion from simple binding is changed to chemical reactivity. 

The opposite case, of over-selecting a patient population, has also been seen recently, and with another ERBB 1 inhibitor— the monoclonal antibody cetuximab. Initial studies were conducted in patients whose tumors had immunohistochemical evidence of EGER expression (25). This ultimately led to inclusion of this criterion in the drug label. It was subsequently found that benefit from cetuximab may also occur in the absence of ERBBl expression (26). 

Nature has required the evolution of usefully selective hosts, and proteins (in the forms of enzymes, receptors, and antibodies) provide them. However, no individual protein molecule lasts in a cell for very long. All proteins are constantly anabolized and catabolized, with constant concentrations achieved via homeostasis. Nature never demanded permanence of its molecular recognition machinery. When we utilize biotic receptors for one-time, batch analytical applications, the receptors clearly meet the useful criterion. However, if a receptor must have an extended lifetime in a sensing device, then we propose that biotic receptors represent the easiest place in which to search instead of the right place to search. If a biotic receptor cannot reasonably be made stable enough to survive weeks of service, then it will not be useful for a sensing application no matter how avid or selective. 

A critical criterion of selection is that the probiotic strain must be tolerated by the immune system and should not provoke the formation of antibodies against the probiotic. This latter property, in conjunction with the ability of some LAB to survive and colonize in the gut, has given rise to further applications, which involve their use as live vectors for oral immunization, i.e., introducing antigens targeting the GALT and aiming to induce a mucosal immune response (Marteau and Rambaud, 1993). 

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